A Study to Evaluate the Effects of Rituximab on Immune Re... | NCT00282308 | Trialant
NCT00282308
Sponsor
Genentech, Inc.
Status
Completed
Last Update Posted
Aug 10, 2017Actual
Enrollment
103Actual
Phase
Phase 2
Conditions
Rheumatoid Arthritis
Interventions
Rituximab
Methotrexate
Methylprednisone
C. albicans
Tetanus toxoid adsorbed booster vaccine
23-valent pneumococcal polysaccharide vaccine
Keyhole limpet hemocyanin
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT00282308
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
U3374g
Secondary IDs
Not provided
Brief Title
A Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
Official Title
A Phase II, Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
Acronym
SIERRA
Organization
Genentech, Inc.INDUSTRY
Status Module
Record Verification Date
Jul 2017
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 23, 2006Actual
Primary Completion Date
Jan 31, 2008Actual
Completion Date
May 28, 2012Actual
First Submitted Date
Jan 24, 2006
First Submission Date that Met QC Criteria
Jan 24, 2006
First Posted Date
Jan 26, 2006Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 5, 2013
Results First Submitted that Met QC Criteria
Aug 19, 2013
Results First Posted Date
Oct 21, 2013Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jul 11, 2017
Last Update Posted Date
Aug 10, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Genentech, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
This was a Phase II, randomized, open-label, multicenter study designed to evaluate the immune response to vaccines after administration of 1000 mg of rituximab in subjects with active rheumatoid arthritis (RA) who were receiving background methotrexate (MTX).
Detailed Description
Patients were randomized to 2 groups in this study: Group A (active group) and Group B (control group). Patients with active rheumatic arthritis treated with rituximab in combination with methotrexate (Group A) were compared with patients treated with methotrexate alone (Group B).
Group A
Group A patients received rituximab 1000 mg intravenously (IV) on Days 3 and 17 of the 36 week treatment period.
At Day 1 and at Week 24, patients received an intradermal injection of 0.1 mL of C. albicans on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin).
At Week 24, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) intramuscular (IM) injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed vaccine.
At Week 28, patients received an IM injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal serotypes were measured at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after administration of the pneumococcal vaccine.
At Weeks 32 and 33, patients received subcutaneous (SC) keyhole limpet hemocyanin 1 mg. Serum anti-keyhole limpet hemocyanin antibody levels were measured at Day 3 immediately prior to the first administration of rituximab, and immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin.
Samples were obtained for the determination of serum rituximab concentration (pharmacokinetics), peripheral blood CD19 counts (pharmacodynamics), and the presence of human anti-chimeric antibodies from all patients in Group A.
Group A patients completed the treatment period at Week 36 and, if qualified, had the option of entering the optional extension re-treatment period. Patients who did not qualify for or who did not choose to receive the optional extension re-treatment entered the approximately 1-year safety follow-up period. After the safety follow-up period, patients who remained peripherally CD19-positive B-cell depleted entered the B-cell follow-up period where they were followed every 12 weeks until their peripheral CD19-positive B cells returned to baseline values or the lower limit of normal, whichever was lower.
Group B
Because the immune response to vaccines was not likely to be influenced by the knowledge of treatment assignment or the time-of-year administration, vaccinations of Group B patients were administered sooner than in the Group A 36 week treatment period.
At Day 1 and at Week 12, patients received an intradermal injection of 0.1 mL of C. albicans on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin).
On Day 1, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) IM injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed vaccine.
At Week 4, patients received an IM injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal serotypes were measured at Day 1, and immediately prior to and 4 weeks after administration of the pneumococcal vaccine.
At Weeks 8 and 9, patients received SC keyhole limpet hemocyanin 1 mg. Serum anti-keyhole limpet hemocyanin antibody levels were measured at Day 1, and immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin.
Upon completion of the Week 12 visit, Group B patients with active rheumatic arthritis, defined as a swollen joint count (SJC) ≥ 4 (66 joint count) and a tender joint count (TJC) ≥ 6 (68 joint count) were eligible for treatment with 2 infusions of rituximab 1000 mg IV, 14 days apart. Patients received the first infusion of rituximab within 2 weeks after completing the Week 12 visit and after the second C. albicans skin test had been read. Patients received methylprednisolone 100 mg IV before each infusion of rituximab.
Group B patients who received treatment with rituximab completed the treatment period through Week 36 and, if qualified, had the option of entering the optional extension re-treatment period. Patients who did not qualify for or who did not choose to receive the optional extension re-treatment entered the approximately 1-year safety follow-up period. After the safety follow-up period, patients who remained peripherally CD19-positive B-cell depleted entered the B-cell follow-up period where they were followed every 12 weeks until their peripheral CD19-positive B cells returned to baseline values or the lower limit of normal, whichever was lower.
Group B patients who did not qualify for and/or did not choose treatment with rituximab completed the study at the end of the primary study period (Week 12).
Conditions Module
Conditions
Rheumatoid Arthritis
Keywords
RA
Rituxan
SIERRA
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
103Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Rituximab + methotrexate (Group A)
Experimental
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Percentage of Patients With a Positive Immune Response to Tetanus Toxoid Adsorbed Booster Vaccine
The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection. For patients with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive immune response was defined as an antibody titer ≥ 0.2 IU/mL. For patients with pre-vaccination tetanus antibody titers ≥ 0.1 IU/mL, a positive immune response to the booster immunization was defined as a 4-fold increase in antibody titer.
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Secondary Outcomes
Measure
Description
Time Frame
Percentage of Patients With a 2-fold Increase in Tetanus Antibody Titers or With Tetanus Antibody Titers ≥ 0.2 IU/mL in Response to Tetanus Toxoid Adsorbed Booster Vaccine
The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Age 18-65 years.
Diagnosis of rheumatoid arthritis (RA) for at least 6 months.
Receiving treatment for RA on an outpatient basis.
Use of methotrexate (MTX) at a dose of 10-25 mg/wk (oral [PO] or subcutaneous [SC]) for at least 12 weeks prior to Day 1, with the dose stable during the last 4 weeks prior to Day 1 (first day of the treatment period).
If taking a background corticosteroid, use of the corticosteroid must be for at least 12 weeks prior to Day 1 at a stable dose during the last 4 weeks prior to Day 1.
If taking one non-steroidal anti-inflammatory drug (NSAID), use of a stable dose for at least 2 weeks prior to Day 1.
Exclusion Criteria:
Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Sjogren's syndrome with RA is permitted.
Bingham CO 3rd, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010 Jan;62(1):64-74. doi: 10.1002/art.25034.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
FG001
Methotrexate (Group B)
Periods
Title
Milestones
Reasons Not Completed
Treatment Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Rituxan
MabThera
Methotrexate
Drug
Methotrexate (Group B)
Rituximab + methotrexate (Group A)
Methylprednisone
Drug
Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab.
Rituximab + methotrexate (Group A)
C. albicans
Biological
Patients received an intradermal injection of C. albicans (0.1 mL) on the volar surface of the forearm.
Methotrexate (Group B)
Rituximab + methotrexate (Group A)
Tetanus toxoid adsorbed booster vaccine
Biological
Patients received an intramuscular injection of the tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) in the deltoid muscle.
Methotrexate (Group B)
Rituximab + methotrexate (Group A)
23-valent pneumococcal polysaccharide vaccine
Biological
Patients received an intramuscular injection of the 23-valent pneumococcal polysaccharide vaccine (0.5 mL) in the deltoid muscle.
Methotrexate (Group B)
Rituximab + methotrexate (Group A)
Keyhole limpet hemocyanin
Biological
Patients received a subcutaneous injection of keyhole limpet hemocyanin (1 mg)
Methotrexate (Group B)
Rituximab + methotrexate (Group A)
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Percentage of Patients With a Positive Immune Response to Each of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Percentage of Patients With a Positive Immune Response to at Least 50% (≥ 6 of 12) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Percentage of Patients With a Positive Immune Response to at Least k (for k = 1, 2, 3, 4, 5) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Serum Level of Anti-tetanus Antibody Measured Immediately Prior to and 4 Weeks After Administration of a Tetanus Toxoid Adsorbed Booster Vaccine
Anti-tetanus antibody was measured in serum samples immediately prior to and 4 weeks after administration of a tetanus toxoid adsorbed booster vaccine. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
Serum Level of Anti-pneumococcal Antibody Measured Immediately Prior to and 4 Weeks After Administration of a 23-valent Pneumococcal Polysaccharide Vaccine
Anti-pneumococcal antibody was measured immediately prior to and 4 weeks after administration of a 23-valent pneumococcal polysaccharide vaccine. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection.
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
Serum Level of Anti-keyhole Limpet Hemocyanin Antibody Measured Immediately Prior to and 4 Weeks After the First Administration of Keyhole Limpet Hemocyanin
Anti-keyhole limpet hemocyanin antibody was measured immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin. The keyhole limpet hemocyanin antibody ELISA assay used keyhole limpet hemocyanin as the plate coat and anti-human IgG-horseradish peroxidase for detection.
Week 32 to Week 36 for Group A and Week 8 to Week 12 for Group B
Percentage of Patients Who Maintained a Positive Response to the C. Albicans Skin Test From Day 1 to Week 24 for Group A or From Day 1 to Week 12 for Group B
Patients received an intradermal injection of C. albicans on the volar surface of the forearm on Day 1 and Week 24 for Group A or on Day 1 and Week 12 for Group B. Forty-eight to 72 hours after injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin). A positive response to the C. albicans skin test was defined as at least 5 mm in diameter of induration.
Day 1 to Week 24 for Group A and Day 1 to Week 12 for Group B
Percentage of Patients in Group A With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24
Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.
Week 24
Paradise Valley
Arizona
85253
United States
Sun Valley Arthritis Center
Peoria
Arizona
85381
United States
Desert Medical Advances
Palm Desert
California
92260
United States
Inland Rheumatology; Clinical Trials, Inc.
Upland
California
91786
United States
Arthritis Associates of South Florida
Delray Beach
Florida
33484
United States
The Arthritis Center
Palm Harbor
Florida
34684
United States
Center For Arthritis; Research Dept
South Miami
Florida
33143
United States
Intermountain Orthopaedics
Boise
Idaho
83702
United States
Northwestern University
Chicago
Illinois
60611
United States
Univ of Chicago
Chicago
Illinois
60637
United States
Evanston Northwestern Healthcare
Evanston
Illinois
United States
Springfield Clinic
Springfield
Illinois
62703
United States
Kentuckiana Center For Better Bone & Joint Healthx
Louisville
Kentucky
40202
United States
Clinical Research Network
Slidell
Louisiana
70458
United States
Johns Hopkins University; Rheumatology
Baltimore
Maryland
21224
United States
Dana Farber Cancer Institute
Boston
Massachusetts
02215
United States
Rheumatology, P.C.; Medical Arts Building
Kalamazoo
Michigan
49009
United States
Borgess Research Institute
Kalamazoo
Michigan
49048
United States
Justus Fiechtner MD - PP
Lansing
Michigan
48910
United States
Center for Rheumatology, State Uni. of New York
Albany
New York
12206
United States
Aair Research Center
Rochester
New York
14618
United States
University of Rochester - Strong Memorial Hospital
Rochester
New York
14642
United States
Physicians East Pa
Greenville
North Carolina
27834
United States
Health Research of Oklahoma, Llc
Oklahoma City
Oklahoma
73103
United States
Oregon Health Sciences Uni
Portland
Oregon
97239
United States
Altoona Arthritis & Osteo Center
Duncansville
Pennsylvania
16635
United States
University of Pennsylvania
Philadelphia
Pennsylvania
19104
United States
Rheumatology Associates
Charleston
South Carolina
29407
United States
Medical University of S. Carolina
Charleston
South Carolina
29425
United States
Arthritis Associates
Hixson
Tennessee
37343
United States
Arthritis Care & Diagnostic Center
Dallas
Texas
75231-4406
United States
Arthritis Clinic of Northern Virginia
Arlington
Virginia
22205
United States
Arthritis Northwest, Spokane
Spokane
Washington
99204
United States
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
FG002
All Patients (Combined Groups A and B)
Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab. Patients received no treatment during the Safety Follow-up Period.
FG00069 subjects
FG00134 subjects
FG0020 subjectsParticipant Flow is reported separately for the treatment groups for this Period.
COMPLETED
FG00065 subjects
FG00128 subjects
FG0020 subjects
NOT COMPLETED
FG0004 subjects
FG0016 subjects
FG0020 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
Subject/Guardian Decision to Withdraw
FG0002 subjects
FG0014 subjects
FG0020 subjects
Adverse Event
FG0000 subjects
FG0012 subjects
FG0020 subjects
Not Treated with Study Drug
FG0001 subjects
FG0010 subjects
FG0020 subjects
Optional Extension Re-treatment Period
Type
Comment
Milestone Data
STARTED
FG0000 subjectsParticipant Flow is reported for the combined treatment groups for this Period.
FG0010 subjectsParticipant Flow is reported for the combined treatment groups for this Period.
FG00278 subjectsNot all patients who completed the Treatment Period entered this Optional Re-treatment Period.
COMPLETED
FG0000 subjects
FG0010 subjects
FG00272 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0026 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0024 subjects
Physician's Decision to Withdraw
FG000
Safety Follow-up Period
Type
Comment
Milestone Data
STARTED
FG0000 subjectsParticipant Flow is reported for the combined treatment groups for this Period.
FG0010 subjectsParticipant Flow is reported for the combined treatment groups for this Period.
FG002100 subjectsSome patients entered this Safety Follow-up Period directly from the Treatment Period.
COMPLETED
FG0000 subjects
FG0010 subjects
FG00281 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG00219 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
Lost to Follow-up
FG000
Safety population: All patients who received any amount of rituximab or any vaccine.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
BG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00068
BG00132
BG002100
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00049.7± 9.60
BG00149.7± 10.51
BG00249.7± 9.85
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00051
BG00125
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Patients With a Positive Immune Response to Tetanus Toxoid Adsorbed Booster Vaccine
The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection. For patients with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive immune response was defined as an antibody titer ≥ 0.2 IU/mL. For patients with pre-vaccination tetanus antibody titers ≥ 0.1 IU/mL, a positive immune response to the booster immunization was defined as a 4-fold increase in antibody titer.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Number
Percentage of patients
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Units
Counts
Participants
OG00064
OG00126
Title
Denominators
Categories
Title
Measurements
OG00039.1
OG00142.3
Secondary
Percentage of Patients With a 2-fold Increase in Tetanus Antibody Titers or With Tetanus Antibody Titers ≥ 0.2 IU/mL in Response to Tetanus Toxoid Adsorbed Booster Vaccine
The immune response to tetanus toxoid adsorbed booster vaccine was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Number
Percentage of patients
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Secondary
Percentage of Patients With a Positive Immune Response to Each of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Number
Percentage of patients
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Secondary
Percentage of Patients With a Positive Immune Response to at Least 50% (≥ 6 of 12) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Number
Percentage of patients
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Secondary
Percentage of Patients With a Positive Immune Response to at Least k (for k = 1, 2, 3, 4, 5) of the 12 Anti-pneumococcal Antibody Serotypes in Response to the 23-valent Pneumococcal Polysaccharide Vaccine
The immune response to each of the 12 anti-pneumococcal antibody serotypes was measured in serum samples immediately prior to and 4 weeks after vaccine administration. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection. A positive immune response against a serotype was defined as a 2-fold increase or an increase of > 1 μg/mL from pre-vaccination levels.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Number
Percentage of patients
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Secondary
Serum Level of Anti-tetanus Antibody Measured Immediately Prior to and 4 Weeks After Administration of a Tetanus Toxoid Adsorbed Booster Vaccine
Anti-tetanus antibody was measured in serum samples immediately prior to and 4 weeks after administration of a tetanus toxoid adsorbed booster vaccine. The tetanus antibody test was an ELISA that used tetanus toxoid as a capturing reagent and alkaline phosphatase-conjugated anti-human IgG (γ) for detection.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Geometric Mean
95% Confidence Interval
IU/mL
Week 24 to Week 28 for Group A and Day 1 to Week 4 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Secondary
Serum Level of Anti-pneumococcal Antibody Measured Immediately Prior to and 4 Weeks After Administration of a 23-valent Pneumococcal Polysaccharide Vaccine
Anti-pneumococcal antibody was measured immediately prior to and 4 weeks after administration of a 23-valent pneumococcal polysaccharide vaccine. The pneumococcal antibody assay was a fluoroimmunoassay that used a Luminex Multiplex platform. Purified capsular polysaccharides isolated from 12 serotypes of S. pneumonia were covalently attached to microbeads and used as a capturing reagent. Phycoerythrin conjugated anti-human IgG was used for detection.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Geometric Mean
95% Confidence Interval
µg/mL
Week 28 to Week 32 for Group A and Week 4 to Week 8 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Secondary
Serum Level of Anti-keyhole Limpet Hemocyanin Antibody Measured Immediately Prior to and 4 Weeks After the First Administration of Keyhole Limpet Hemocyanin
Anti-keyhole limpet hemocyanin antibody was measured immediately prior to and 4 weeks after the first administration of keyhole limpet hemocyanin. The keyhole limpet hemocyanin antibody ELISA assay used keyhole limpet hemocyanin as the plate coat and anti-human IgG-horseradish peroxidase for detection.
Immune response per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion and any vaccine and had pre-vaccination and 4-week post-vaccination blood samples. Group B - All patients randomized to Group B who received any vaccine and had pre-vaccination and 4-week post-vaccination blood samples.
Posted
Geometric Mean
95% Confidence Interval
IU/mL
Week 32 to Week 36 for Group A and Week 8 to Week 12 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Secondary
Percentage of Patients Who Maintained a Positive Response to the C. Albicans Skin Test From Day 1 to Week 24 for Group A or From Day 1 to Week 12 for Group B
Patients received an intradermal injection of C. albicans on the volar surface of the forearm on Day 1 and Week 24 for Group A or on Day 1 and Week 12 for Group B. Forty-eight to 72 hours after injection, patients were evaluated for a delayed-type hypersensitivity response by measuring the diameter of induration (palpable raised, hardened area of the forearm skin). A positive response to the C. albicans skin test was defined as at least 5 mm in diameter of induration.
Skin test per-protocol population: Group A - All patients randomized to Group A who received any rituximab infusion, had Day 1 and Week 24 skin tests, and who provided complete diameter of induration readings. Group B - All patients randomized to Group B who had Day 1 and Week 12 skin tests and who provided complete diameter of induration readings.
Posted
Number
Percentage of patients
Day 1 to Week 24 for Group A and Day 1 to Week 12 for Group B
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
OG001
Methotrexate (Group B)
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Secondary
Percentage of Patients in Group A With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24
Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and C reactive protein or, if missing, erythrocyte sedimentation rate.
Safety population: All patients who received any amount of rituximab or any vaccine. Since only limited efficacy data were collected in this study, the parameters necessary to calculate the ACR20/50/70 responses were only available for patients in Group A.
Posted
Number
Percentage of patients
Week 24
ID
Title
Description
OG000
Rituximab + Methotrexate (Group A)
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
Time Frame
Adverse events were reported from Weeks 1-36 for Group A and Weeks 1-24 for Group B of the treatment period, Weeks 1-6 of the optional extension retreatment period, and Weeks 1-48 of the safety follow-up period (maximum of up to 90 weeks).
Description
Safety population: All patients who received any amount of rituximab or any vaccine.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Rituximab + Methotrexate (Group A) - Treatment Period
Patients received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
3
68
51
68
EG001
Methotrexate (Group B) - Treatment Period
Patients received methotrexate 10-25 mg/wk orally or subcutaneously during the Treatment Period.
2
32
19
32
EG002
Group A - Optional Extension Re-treatment Period
Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab.
2
52
7
52
EG003
Group B - Optional Extension Re-treatment Period
Patients who qualified for re-treatment received 2 intravenous infusions of rituximab 1000 mg, 14 days apart + methotrexate 10-25 mg/week orally or subcutaneously. Patients received methylprednisolone 100 mg intravenously before each infusion of rituximab.
2
26
13
26
EG004
Group A - Safety Follow-up Period
Patients received no treatment during the Safety Follow-up Period.
3
68
19
68
EG005
Group B - Safety Follow-up Period
Patients received no treatment during the Safety Follow-up Period.
1
32
11
32
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Coronary artery disease
Cardiac disorders
Systematic Assessment
EG0001 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG0030 affected26 at risk
EG0040 affected68 at risk
EG0050 affected32 at risk
Chest pain
General disorders
Systematic Assessment
EG0001 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Hip fracture
Infections and infestations
Systematic Assessment
EG0001 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Ovarian cyst
Reproductive system and breast disorders
Systematic Assessment
EG0000 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Amaurosis fugax
Eye disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0021 affected52 at risk
EG003
Pyelonephritis
Infections and infestations
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0021 affected52 at risk
EG003
Ovarian cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Thyroid cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Bipolar disorder
Psychiatric disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
Systematic Assessment
EG0007 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG0030 affected26 at risk
EG0040 affected68 at risk
EG0050 affected32 at risk
Diarrhoea
Gastrointestinal disorders
Systematic Assessment
EG0005 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Upper respiratory tract infection
Infections and infestations
Systematic Assessment
EG0007 affected68 at risk
EG0012 affected32 at risk
EG0021 affected52 at risk
EG003
Sinusitis
Infections and infestations
Systematic Assessment
EG0005 affected68 at risk
EG0010 affected32 at risk
EG0022 affected52 at risk
EG003
Influenza
Infections and infestations
Systematic Assessment
EG0005 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG00012 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0008 affected68 at risk
EG0011 affected32 at risk
EG0022 affected52 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0004 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Headache
Nervous system disorders
Systematic Assessment
EG0009 affected68 at risk
EG0013 affected32 at risk
EG0020 affected52 at risk
EG003
Insomnia
Psychiatric disorders
Systematic Assessment
EG0003 affected68 at risk
EG0012 affected32 at risk
EG0020 affected52 at risk
EG003
Throat irritation
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0005 affected68 at risk
EG0012 affected32 at risk
EG0020 affected52 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0005 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0007 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0022 affected52 at risk
EG003
Urinary tract infection
Infections and infestations
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Bronchitis
Infections and infestations
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Ear pruritus
Ear and labyrinth disorders
Systematic Assessment
EG0001 affected68 at risk
EG0013 affected32 at risk
EG0020 affected52 at risk
EG003
Fatigue
General disorders
Systematic Assessment
EG0004 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Feeling hot
General disorders
Systematic Assessment
EG0002 affected68 at risk
EG0012 affected32 at risk
EG0020 affected52 at risk
EG003
Oedema peripheral
General disorders
Systematic Assessment
EG0004 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Genital herpes
Infections and infestations
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0004 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Dizziness
Nervous system disorders
Systematic Assessment
EG0004 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Respiratory tract congestion
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
Systematic Assessment
EG0009 affected68 at risk
EG0013 affected32 at risk
EG0020 affected52 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
Systematic Assessment
EG0004 affected68 at risk
EG0012 affected32 at risk
EG0020 affected52 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
Systematic Assessment
EG0005 affected68 at risk
EG0011 affected32 at risk
EG0020 affected52 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
Systematic Assessment
EG0001 affected68 at risk
EG0013 affected32 at risk
EG0020 affected52 at risk
EG003
Flushing
Vascular disorders
Systematic Assessment
EG0004 affected68 at risk
EG0010 affected32 at risk
EG0020 affected52 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.